SREBP-1c Gene Silencing can Decrease Lipid Deposits in Bovine Hepatocytes Cultured <b><i>in Vitro</i></b>

Abstract

Background: Fatty liver is a major metabolic disorder that occurs during early lactation in high-producing dairy cows. Sterol regulatory element-binding protein-1c (SREBP-1c) is an important transcription factor that regulates lipid synthesis by regulating the expression of lipid metabolism genes. Methods: In this study, we reduced the expression of SREBP-1c by adenovirus-mediated SREBP-1c with a low expression vector (AD-GFP-SREBP-1c) to study the effects of SREBP-1c on lipid deposits in bovine hepatocytes. The expression levels and enzyme activities of SERBP-1c and its target genes were determined by real-time PCR, western blot, and ELISA. Results: These results showed that Ad-GFP-SREBP-1c could inhibit SREBP-1c expression. The expression of the lipid synthesis enzyme acetyl-CoA carboxylase (ACC) was down-regulated. The expression levels of the lipid oxidation enzymes long-chain fatty acyl-COA synthetase (ACSL-1), carnitine palmitoyltransferase І (CPT-І), carnitine palmitoyltransferase II (CPT- II), and β-hydroxyacyl-CoA-DH (HADH) were significantly elevated. Furthermore, the expression levels of factors involved in the assembly and transport of very low-density lipoproteins (VLDLs), such as apolipoprotein B100 (ApoB), apolipoprotein E (ApoE), and microsomal triglyceride transfer protein (MTTP) were decreased comparison with the negative control and the blank control groups, but the low-density lipoprotein receptor (LDLR) was elevated. The concentrations of TG (triglyceride) and VLDL were also reduced. Conclusion: These data suggest that low SREBP-1c expression can decrease lipid synthesis, increase lipid oxidation, and decrease the TG and VLDL content in bovine hepatocytes.

Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis

“…Members of long chain acyl-CoA synthetase (ACSL) family (ACSL1, ACSL3, ACSL4, and ACSL6) dramatically prevailed in these genes. Because of ACSLs' essential role in fatty acid oxidation [42, 43], LPIN1 is capable of selectively activating fatty acid oxidation and mitochondrial oxidative phosphorylation, which have already been proved by gain-of-function and loss-of-function strategies [40, 44–46]. Downregulated LPIN1, however, prevent the fatty acid degradation in an ACSL-dependent way.…”

Up-Regulation Mttp and Apob Gene Expression in Rat Liver is Related to Post-Lipectomy Hypertriglyceridemia

“…The data presented on Figure 4 suggests that this was the case in our lipectomized animals. Moreover, HNF1α is also involved in the regulation of Srebf gene [48], and the product of this gene (SREBP-1) is a key regulator of lipogenesis [49]. Therefore, the up-regulation of Hnf1a is likely associated with the enhancement of Srebf gene expression in the livers of lipectomized rats.…”

SREBP-1c overactivates ROS-mediated hepatic NF-κB inflammatory pathway in dairy cows with fatty liver

“…A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 21 knockdown by siRNA did not significantly influence the NEFA-induced activation of the NF-κB pathway or target the inflammatory cytokines IL-6, TNF-α, or IL-1β. Furthermore, ROS content was measured also in the NEFA and NEFA+siTLR4 groups, and no significant differences were observed between these two groups.…”

“…A previous study demonstrated that dairy cows with fatty liver presented strong inflammation [21]. To evaluate the inflammatory levels of cows with fatty liver, blood concentrations of IL-1β, IL-6 and TNF-α were measured in healthy cows and in cows with hepatic steatosis (mild, moderate and severe fatty liver).…”